A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.

ABSTRACT: Artemisinin-based combination therapy (ACT) is the mainstay of effective treatment of Plasmodium falciparum malaria. However, the long-term utility of ACTs is imperiled by widespread partial artemisinin resistance in Southeast Asia and its recent emergence in parts of East Africa. This underscores the need to identify chemotypes with new modes of action (MoAs) to circumvent resistance to ACTs. In this study, we characterized the asexual blood stage antiplasmodial activity and resistance mechanisms of LDT-623, a 4-aminoquinoline (4-AQ). We also detected LDT-623 activity against multiple stages (liver schizonts, stage IV-V gametocytes, and ookinetes) of Plasmodium's life cycle, a feature unlike other 4-AQs such as chloroquine (CQ) and piperaquine (PPQ). Using heme fractionation profiling and

SUBMITTER: Ferreira LT 

PROVIDER: S-EPMC11521309 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature